[14090-83-6] · C9H10O3S · Methyl 2-(Phenylsulfinyl)acetate · (MW 198.26)
(synthetic equivalent of a vinyl organometallic species; undergoes addition/elimination to aldehydes to give conjugated dienoates or 4-hydroxy (2E)-enoates)
Physical Data: mp 53-55 °C; bp 130-131 °C/0.5 mmHg.
Form Supplied in: solid; widely available.
Handling, Storage, and Precautions: fp >100 °C.
The sodium and lithium enolates of methyl 2-(phenylsulfinyl)acetate are very stable and tend not to react with aldehydes under normal conditions; however, the Knovenagel amine-catalyzed condensation1,2 occurs under mild conditions to give 3-aryl-2-(phenylsulfinyl)(2E)-propenoate methyl esters stereoselectively (eq 1) in a 98:2 (E:Z) ratio as determined by Tf2O/dimethyl sulfide reduction followed by GLC analysis. These compounds are useful because they are powerful dienophiles in a variety of Diels-Alder reactions.
Under similar Knovenagel conditions, methyl 2-(phenylsulfinyl)acetate can undergo addition to afford the sulfinyl condensation product; base-catalyzed deconjugation, a [2,3]-sigmatropic shift, and hydrolysis of the sulfenate ester intermediate then affords 4-hydroxy (2E)-enoates3-5 in one pot (eqs 2 and 3).
Trost et al.5 have demonstrated that the palladium-catalyzed addition of methyl 2-(phenylsulfinyl)acetate to palladium p-allyl complexes gives intermediate allylsulfinates, which undergo a standard thermal elimination of the sulfoxide group to afford 2,4-dienoates efficiently from alkenes (eqs 4 and 5).
Despite the low reactivity of the enolates, methyl 2-(phenylsulfinyl)acetate can be induced to undergo nucleophilic attack. Methyl cyclobutenecarboxylate6 can be prepared by deprotonation of the reagent with a solution of 2 equiv of Sodium Hydride and 1,3-Diiodopropane in DMF to give the cyclic product; pyrolysis at 160 °C affords the cyclobutene product in a low (39%) overall yield (eq 6).
Benzylic bromides also undergo an efficient one-pot alkylation/elimination using Potassium Carbonate in the presence of a phase-transfer catalyst such as aliquat-336 in DMF to afford trans-unsaturated esters in good yields (eq 7).7
Treatment of methyl 2-(phenylsulfinyl)acetate with Tin(II) Trifluoromethanesulfonate effects conversion of the sulfoxide group to the Pummerer intermediate. This reacts with silyl enol ethers in the presence of N-(Trimethylsilyl)imidazole to afford 1,4-dicarbonyl compounds8 containing a phenylthio group, which can be oxidized and thermally eliminated to give unsaturated dicarbonyl compounds or reductively removed to give the saturated analogs (eq 8).
The potassium salt of methyl 2-(phenylsulfinyl)acetate can be induced to undergo a Michael addition in the presence of 18-Crown-6. Subsequent thermal elimination of the sulfoxide group in refluxing xylenes affords the a,b-unsaturated enone, via equilibration of the double bond into conjugation with the ketone. This reaction constitutes the synthetic equivalent of an acetate anion addition to an a,b-unsaturated system with retention of unsaturation (eq 9).9
A tandem Michael addition/enolate acylation reaction with a,b-unsaturated methyl ketones is possible in the presence of Magnesium Methoxide, giving rise to a 1,3-diketocyclohexane system; on heating, this eliminates the sulfoxide group to give an aromatic resorcinol system (eq 10).10
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ, USA